Erythropoietin (EPO) is a kidney-derived glycoprotein hormone that stimulates red blood cell formation. Recombinant human EPO is widely used to stimulate erythropoiesis in patients with anemia and had world-wide sales in excess of $3 billion during 1997. We propose to create modified EPO proteins that are equal or superior to natural EPO at stimulating erythropoiesis in vivo, but which require less frequent dosing, on the order of once per week to once per month. During Phase I we identified sites in EPO that can be modified without affecting the protein's in vitro bioactivity. During Phase II, we will manufacture sufficient quantities of the modified EPO proteins for testing in pharmacokinetic and animal efficacy experiments. The improved characteristics of the novel EPO proteins will reduce the amount of EPO required per patient, improve patient compliance and quality of life and result in considerable cost savings to patients and healthcare providers. EPO is a member of a large family of structurally related growth factors and cytokines. Information gained from these studies will aid in creating long-acting versions of other members of this gene family for use in treating cancer, infectious disease and hematopoietic disorders. PROPOSED COMMERCIAL APPLICATIONS: Recombinant human EPO is used to restore red blood cell production in patients with anemia resulting from renal failure, chemotherapy and drug complications. Recombinant EPO had worldwide sales in excess of $3 billion in 1997. The modified EPO proteins under development will require much less frequent dosing, providing significant cost savings to patients and healthcare providers. Additional benefits may include significantly lower manufacturing costs, improved drug efficacy and improved patient quality of life.